Racemic bupivacaine is an effective long-acting local anaesthetic, and may be given as an epidural. However, racernic bupivacaine is cardiotoxic, having depressant electrophysiological and mechanical effects on the heart. It should therefore be used with caution in cardiac-compromised patients, and the use of high doses and high concentrations is contraindicated.
In particular, bupivacaine has produced death in a number of patients, including women in childbirth and when used in the Bier's block technique. Although the incidence of death has been relatively small, the concern has been sufficient to stop the use of 0.75% bupivacaine for obstetrics and the proscribing of bupivacaine for use in Bier's blocks.
In addition, due to its mode of action, directly on the nervous system, at higher doses, bupivacaine is known to have undesirable central nervous system (CNS) side-effects which, prima facie, are connected to its anaesthetic activity. Indeed, the occurrence of CNS side-effects is one of the major factors limiting the use of this drug in normal clinical practice employing techniques such as local infiltration, nerve block, field block, epidural and spinal blocks.
It has been suggested that levobupivacaine is less cardiotoxic than dextrobupivacaine and racemic bupivacaine. See, for example, Vanhoutte et al, Br. J. Pharmacol. 103: 1275-1281 (1991), and Denson et al, Regional Anaesthesia 17:311-316 (1992). However, these reports are based on work in vitro, and cannot necessarily be extrapolated to any mammals, and certainly not to humans.
The effective utility of levobupivacaine in man, in vivo, is evidenced for the first time in WO-A-9510276, WO-A-9510277 and Gristwood et al, Exp. Opin. Invest. Drugs 3(11):1209-12 (1994). The latter documents indicate the potential utility of levobupivacaine in obstetrics, in part at least because of reduced CNS side-effects.
Gristwood et al also disclose that bupivacaine has "a beneficial ratio of sensory to motor blockade. This ratio is particularly important for obstetric use as it affords appropriate sensory block and yet allows women to consciously participate in the childbirth". Gristwood et al then report experiments comparing bupivacaine and levobupivacaine, and conclude that a "preliminary analysis of the data suggests that in terms of sensory block levobupivacaine has comparable efficacy to bupivacaine, with the duration of sensory block for 0.25% levobupivacaine being similar to that seen with bupivacaine 0.25%".
In many cases of surgery, there are both economic and practical reasons why hospital care should be relatively short. In the past, even for minor surgery, the patient might have been starved, given a full anaesthetic prior to surgery, and subsequently allowed to recover, involving hospital care for, say, 1 week. It is now realised that the same surgical procedure might be carried out with patient compliance, e.g. a coronary bypass may be conducted under local anaesthetic, with discharge after only 24 hours. This means that incisions are generally smaller, hospital beds can be made available more quickly, reduces patient stress and post-operative morbidity can be reduced, and the likelihood of good post-operative recovery is enhanced. Such "outpatient", "daycare" or "ambulatory" surgery requires the use of an anaesthetic that has a good ratio of sensory to motor blockade.
WO-A-9500148 discloses that ropivacaine salts provide sensory block and "minimal motor blockade". It is suggested that this effect is desirable, because reduced motor blockade (compared to bupivacaine) allows the patient to move, say, legs soon after operation.